Journal of Stem Cell Research & Therapy

Short activating RNA (saRNA) targeting C/EBPA significantly inhibits cell proliferation of undifferentiated cancer cells

4^th International Conference and Exhibition on Cell & Gene Therapy

August 10-12, 2015 London, UK

Nagy Habib1, V Reebye1, P J Mintz1, P Sætrom2, P Swiderski3, N Kasahara4, J P Nicholls1 and J J Rossi3

Posters-Accepted Abstracts: J Stem Cell Res Ther

Abstract:

In general, ‘poorly’ differentiated tumors have a worse prognosis when compared to more ‘well’ differentiated ones. Therefore,
the use of a biological agent that could promote differentiation might have a therapeutic advantage. CCAAT enhancer binding
protein alpha (C/EBPα) is a transcription factor known to be involved in the regulation of cell differentiation in a number of
tissue types and has reported to inhibit the development of hepatocellular carcinoma. Here we report the effect of stimulation
of C/EBPα expression by a specific small activating RNA (saRNA) on a panel of cell lines representing both well-differentiated
and poorly-differentiated cancer cell types. The C/EBPα-saRNA inhibited proliferation of poorly differentiated small cell lung
cancer and pancreatic cancer cell lines compared to treatment with scrambled double-stranded RNA controls. However C/
EBPα-saRNA was not as effective in suppressing proliferation in well-differentiated insulinoma and breast cancer (MCF7)
cell lines. Comparison of endogenous levels of C/EBPα, using qPCR and Western blots, showed that undifferentiated tumor
cell lines expressed lower levels of C/EBPα when compared to the well-differentiated tumor types. Our results suggest that
saRNA mediated stimulation of C/EBPα, could be of potential therapeutic value, especially in poorly differentiated cancers.
Furthermore, intracellular expression levels of C/EBPα could be an important prognostic factor for predicting the therapeutic
response in poor or un-differentiated tumors.

Biography :

Nagy Habib, Professor of Hepatobiliary Surgery at Imperial College London is a Translational Researcher who pioneered the first clinical trial in the use of adenovirus
and plasmid for the treatment of liver cancer, and the use of plasmid gene therapy in the hydrodynamic gene delivery. He was also the first to publish from the West
a clinical trial on the use of adult bone marrow-derived stem cells for the treatment of patients with liver insufficiency. He has published on the evolution of molecular
biology of tumors (oncogene, tumor suppressor gene, and epigenetic modification), gene therapy, stem cell therapy, saRNA and RNAaptamers.